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Pediatric generalized anxiety disorder (GAD) is characterized by excessive and uncontrollable worry about a variety of events and is accompanied by physical symptoms such as headaches, tension, restlessness, gastrointestinal distress, and heart palpitations. Symptoms impose marked distress and interfere with social, emotional, and educational functioning. GAD occurs in over 10% of children and adolescents, has an average age of onset of 8.5 years, and is more often reported in girls. Common co-occurring conditions include separation anxiety disorder and social phobia. Assessment involves a multi-informant, multi-method approach involving the child, parents, and school teachers. A clinical interview should be conducted to assess for the three primary ways anxiety presents: behaviors, thoughts, and somatic symptoms. Several semi-structured diagnostic interviews are available, and the Anxiety Disorders Interview Schedule is increasingly used. Rating scales completed by the patient, caregivers, and teachers provide useful information for diagnosis and symptom monitoring. Several scales are available to assess patients for the Diagnostic and Statistical Manual of Mental Disorders (4th Edition) GAD diagnosis; however, instruments generally cannot distinguish children with GAD from children with similar anxiety disorders. Both cognitive-behavioral therapy (CBT) and selective serotonin reuptake inhibitors (SSRIs) have demonstrated efficacy for the treatment of pediatric anxiety disorders including GAD. Evidence suggests that the combination of CBT plus sertraline offers additional benefit compared with either treatment alone. With pharmacotherapy, systematic tracking of treatment-emergent adverse events such as headaches, stomach aches, behavioral activation, worsening symptoms, and emerging suicidal thoughts is important. Recommended starting doses are fluvoxamine 25 mg/day, fluoxetine 10 mg/day, and sertraline 25 mg/day, though lower starting doses are possible. Dosing can be adjusted as often as weekly with the goal of achieving a high-quality response, while minimizing side effects. Long-term treatment with medication has not been well studied; however, to achieve optimal long-term outcome extended use of medication may be required. It is recommended to continue medication for approximately 1 year following remission in symptoms, and when discontinuing medication to choose a stress-free time of the year. If symptoms return, medication re-initiation should be considered seriously.
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PMID:Pediatric generalized anxiety disorder: epidemiology, diagnosis, and management. 1944 46

Duloxetine (Cymbalta(R)) is a potent serotonin and noradrenaline (norepinephrine) reuptake inhibitor (SNRI) in the CNS. It is indicated for the treatment of generalized anxiety disorder (GAD) as well as other indications. In patients with GAD of at least moderate severity, oral duloxetine 60-120 mg once daily was effective with regard to improvement from baseline in assessments of anxiety and functional impairment, and numerous other clinical endpoints. Longer-term duloxetine 60-120 mg once daily also demonstrated efficacy in preventing or delaying relapse in responders among patients with GAD. In addition, duloxetine was generally well tolerated, with most adverse events being of mild to moderate severity in patients with GAD in short- and longer-term trials. Additional comparative and pharmacoeconomic studies are required to position duloxetine among other selective serotonin reuptake inhibitors and SNRIs. However, available clinical data, and current treatment guidelines, indicate that duloxetine is an effective first-line treatment option for the management of GAD. Duloxetine is a potent and selective inhibitor of serotonin and noradrenaline transporters, and a weak inhibitor of dopamine transporters. It has a low affinity for neuronal receptors, such as alpha(1)- and alpha(2)-adrenergic, dopamine D(2), histamine H(1), muscarinic, opioid and serotonin receptors, as well as ion channel binding sites and other neurotransmitter transporters, such as choline and GABA transporters. It does not inhibit monoamine oxidase types A or B. The pharmacokinetics of duloxetine in healthy volunteers were dose proportional over the range of 40-120 mg once daily. Steady state was typically reached by day 3 of administration. Duloxetine may be administered without regard to food or time of day. Duloxetine is highly protein bound and is widely distributed throughout tissues. It is rapidly and extensively metabolized in the liver by cytochrome P450 (CYP) 1A2 and 2D6, and its numerous metabolites, which are inactive, are mainly excreted in the urine. The mean elimination half-life of duloxetine is approximately 12 hours. Duloxetine is a substrate for CYP1A2 and CYP2D6 and a moderate inhibitor of CYP2D6. Concomitant use of duloxetine and potent CYP1A2 inhibitors should be avoided and duloxetine should be used with caution in patients receiving drugs that are extensively metabolized by CYP2D6, particularly those with a narrow therapeutic index. Duloxetine was effective in the short-term treatment of patients with primary GAD of at least moderate severity. In four randomized, double-blind, placebo-controlled, multicentre, phase III trials, duloxetine 60-120 mg once daily for 9 or 10 weeks was significantly more effective than placebo with regard to the primary endpoint of mean change in Hamilton Anxiety Rating Scale (HAM-A) total score from baseline to study endpoint. In addition, all other endpoints were generally improved from baseline to a greater extent with duloxetine 60-120 mg once daily than with placebo. Duloxetine also improved patient role functioning (assessed using Sheehan Disability Scale global impairment functioning scores), health-related quality of life and patient well-being compared with placebo. Duloxetine was effective in patients with GAD who were aged >/=65 years. Pooled results of data from the two short-term efficacy trials that also included an active comparator arm showed that the mean change in HAM-A scores with duloxetine relative to placebo were of the same magnitude as those with venlafaxine extended release versus placebo. Duloxetine 60-120 mg once daily was also more effective than placebo in preventing or delaying relapse in responders to duloxetine in a longer-term study. In this study, patients with GAD received duloxetine during a 26-week, open-label, acute treatment phase and responders were then randomized to continue on duloxetine or receive placebo during a 26-week, double-blind, continuation phase. Time to relapse was significantly longer in duloxetine recipients than in placebo recipients. In addition, significantly fewer duloxetine recipients than placebo recipients relapsed during the double-blind phase of the trial and more duloxetine recipients achieved remission. Short- (9-10 weeks) and longer-term (52 weeks) treatment with duloxetine 60-120 mg once daily was generally well tolerated in patients with GAD, with the majority of adverse events being of mild to moderate severity. Nausea, dry mouth, headache, constipation, dizziness and fatigue were among the most common treatment-emergent adverse events. The adverse event profile of duloxetine did not differ with dose or treatment duration. Significantly more patients receiving short-term duloxetine than placebo discontinued treatment because of an adverse event, with nausea being the only event that resulted in significantly more treatment discontinuations in duloxetine recipients than in placebo recipients. Serious adverse events were uncommon with both short- and longer-term duloxetine treatment. Two episodes of attempted suicide and one episode of completed suicide occurred in duloxetine recipients during the 24-week open-label phase of a longer-term trial. No deaths or suicides were reported in any of the short-term trials. Discontinuation-emergent adverse events, most commonly nausea and dizziness, occurred in up to one-third of duloxetine recipients in the short-term trials.
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PMID:Duloxetine: a review of its use in the treatment of generalized anxiety disorder. 1948 Apr 70

A growing body of literature has implicated comorbid psychopathology as a potential risk factor for the chronification of migraine. Of the psychiatric disorders, depressive and anxiety disorders have been most consistently associated with the chronification of migraine. A shared dysfunction of the serotonergic system, medication overuse, and psychological factors have been proposed to mediate this relationship, although the responsible mechanisms are still largely unclear. This article overviews literature on psychiatric comorbidities and migraine chronification, considers mechanisms underlying this relationship, and notes directions for future clinical and empirical work.
Curr Pain Headache Rep 2009 Aug
PMID:Psychiatric comorbidities and migraine chronification. 1958 98

ABSTRACT Migraine is one of the most common causes of pain and headache seen in the offices of pediatricians and child neurologists. In addition to standard antimigraine treatments (ergots, cyproheptadine), several types of psychotropic medication have been used in the treatment of migraine, primarily prophylactically, with varying degrees of success. Although there is some evidence of their efficacy in treating migraine in adults, there are relatively few studies of their efficacy or safety with children. The authors review the literature on childhood migraine, its relationship to mood and anxiety disorders, modern pathophysiological theories, and current treatment approaches. Despite the widespread use of propranolol, further studies are needed before beta blockers can be considered an effective prophylactic agent in childhood migraine. Antidepressants seem promising in adolescents and children, but more controlled studies are needed to determine their long-term efficacy in children and adolescents. Antidepressant agents with mixed serotonin and norepinephrine action (e.g., amitriptyline) seem more effective than the more selective agents in adults, but it generally remains to be seen whether antimigraine medications that are effective in adults will be equally useful in children and adolescents. Studies on mood and anxiety disorders in children and adolescents might be usefully extended to evaluate migraine headaches.
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PMID:Psychopharmacological management of migraine in children and adolescents. 1963 Jun 31

The efficacy and tolerability of extended-release quetiapine fumarate (quetiapine XR) once-daily monotherapy in generalized anxiety disorder (GAD) was assessed. This multicentre, double-blind, randomized, placebo- and active-controlled, phase III trial consisted of a 1- to 4-wk enrolment/wash-out period and a 10-wk (8-wk active treatment, 2-wk post-treatment drug-discontinuation) study period; 873 patients were randomized to 50 mg or 150 mg quetiapine XR, 20 mg paroxetine, or placebo. Primary endpoint was change from randomization at week 8 in Hamilton Rating Scale for Anxiety (HAMA) total score. At week 8, all active agents produced significant improvements in HAMA total and psychic subscale scores vs. placebo; HAMA somatic subscale scores were significantly reduced only by 150 mg quetiapine XR. Significant separation from placebo (-2.90) in HAMA total score was observed at day 4 for 50 mg quetiapine XR (-4.43, p<0.001) and 150 mg quetiapine XR (-3.86, p<0.05), but not for paroxetine (-2.69). Remission (HAMA total score 7) rates at week 8 were significantly higher for 150 mg quetiapine XR (42.6%, p<0.01) and paroxetine (38.8%, p<0.05) vs. placebo (27.2%). The most common adverse events (AEs) were dry mouth, somnolence, fatigue, dizziness, and headache, for quetiapine XR, and nausea, headache, dizziness for paroxetine. A lower proportion of patients reported sexual dysfunction with quetiapine XR [0.9% (50 mg), 1.8% (150 mg)] than with placebo (2.3%) or paroxetine (7.4%). The incidence of AEs potentially related to extrapyramidal symptoms was: quetiapine XR: 50 mg, 6.8%, 150 mg, 5.0%; placebo, 1.8%; and paroxetine, 8.4%. Once-daily quetiapine XR is an effective and generally well-tolerated treatment for patients with GAD, with symptom improvement seen as early as day 4.
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PMID:Extended-release quetiapine fumarate (quetiapine XR): a once-daily monotherapy effective in generalized anxiety disorder. Data from a randomized, double-blind, placebo- and active-controlled study. 1969 7

Functional somatic syndromes (FSSs) are common in dental as well as medical practice. Many patients with unexplained symptoms in oro-maxillo-facial areas visit dentists, but they are not diagnosed and treated properly. Temporomandibular disorder, atypical facial pain, and glossodynia (burning mouth syndrome) are included in dental FSSs. These diseases overlap with each other and with FSSs in other organs, such as myofacial pain syndrome, tension-type headache, fibromyalgia, and chronic fatigue syndrome. They coexist with mental disorders, such as anxiety disorder, mood disorder, and somatoform disorder. Multidisciplinary and holistic approaches should be applied to dental FSSs; pharmacological therapy (antidepressants), physical therapy, and cognitive-behavioral therapy. Clinicians have to support a patient in"enjoying his/her life with symptoms". Dental specialists in "oral medicine" with psychosomatic viewpoints are now required.
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PMID:[Functional somatic syndrome in dental practice]. 1976 11

A number of comorbid disorders, behavioural traits and associated risk factors in patients with migraine are known to increase the risk of complications such as ischaemic vascular events and chronic migraine, a syndrome that is more disabling and resistant to treatment with acute and preventative medications than episodic migraine. Reduction of cardiovascular risk factors, smoking cessation and use of non-oestrogen-containing oral contraceptives in female patients are beneficial strategies to reduce the risk of ischaemic events in patients with migraine (especially those with aura). Attack frequency, acute medication overuse, obesity and coexisting depression and anxiety disorders are particularly strong but potentially modifiable independent risk factors for progression to chronic migraine. Identifying and managing comorbidities and associated risk factors for complications of migraine are likely to require an integrated disease management strategy involving several disciplines and allied health services. Such a disease-oriented model of care may potentially interrupt the cycle of progression and disability and improve quality of life for patients with migraine.
Cephalalgia 2009 Dec
PMID:Review of comorbidities and risk factors for the development of migraine complications (infarct and chronic migraine). 2001 49

According to the analysis in pediatrics, 5.8% of children aged equal or more than 3 years attended pediatric outpatient clinics had psychosomatic problems. The logistic regression analysis demonstrated that children with psychosomatic problems had complained more chronic fatigue (odds ratio: 2.55), headache (2.42) and recurrent abdominal pain(2.03) in comparison with controls. The other study showed many children with school phobia had trouble with class mates and complained somatoform disorders. Working with somatizing patients and their parents can be frustrating the pediatrician, and comorbid psychiatric disorders are common in these patients. To get good carryover, the psychiatric consult is needed if they have suffered from major depressive disorder, and other anxiety disorders.
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PMID:[Care continuity for children with psychosomatic disorders]. 2007 98

Self-hypnosis training represents a rapid, cost-effective, nonaddictive and safe alternative to medication for the treatment of anxiety-related conditions. Here we provide a review of the experimental literature on the use of self-hypnosis in the treatment of anxiety and stress-related disorders, including anxiety associated with cancer, surgery, burns and medical/dental procedures. An overview of research is also provided with regard to self-hypnotic treatment of anxiety-related disorders, such as tension headaches, migraines and irritable bowel syndrome. The tremendous volume of research provides compelling evidence that hypnosis is an efficacious treatment for state anxiety (e.g., prior to tests, surgery and medical procedures) and anxiety-related disorders, such as headaches and irritable bowel syndrome. Although six studies demonstrate changes in trait anxiety, this review recommends that further randomized controlled outcome studies are needed on the hypnotic treatment of generalized anxiety disorder and in documenting changes in trait anxiety. Recommendations are made for selecting clinical referral sources.
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PMID:Hypnosis in the treatment of anxiety- and stress-related disorders. 2013 82

To examine associations among Puerto Rican children's physical health problems and children's internalizing disorders, parental psychopathology and acculturative stress, and family factors. A population-based probability sample of 2491 Puerto Rican children, aged between 5 and 13 years, and caregivers from the South Bronx and the U.S. Commonwealth of Puerto Rico participated in this study. The parent version of the Diagnostic Interview Schedule for Children-IV was used to assess children's internalizing disorders. Children's anxiety disorders, parental psychopathology, and acculturative stress were associated with childhood asthma, abdominal pain, and headaches. Children's depressive disorders, maternal acceptance, and family functioning were associated with abdominal pain and headaches. Parents of children living in Puerto Rico were more likely to report physical health problems in their children than in the Bronx. Children's internalizing disorders, parental psychopathology, and acculturative stress may be important areas to target among Puerto Rican children with physical health problems.
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PMID:Child and family psychiatric and psychological factors associated with child physical health problems: results from the Boricua youth study. 2038 56


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